134 research outputs found

    Electron-wall interaction in Hall thrusters

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    Electron-wall interaction effects in Hall thrusters are studied through measurements of the plasma response to variations of the thruster channel width and the discharge voltage. The discharge voltage threshold is shown to separate two thruster regimes. Below this threshold, the electron energy gain is constant in the acceleration region and therefore, secondary electron emission (SEE) from the channel walls is insufficient to enhance electron energy losses at the channel walls. Above this voltage threshold, the maximum electron temperature saturates. This result seemingly agrees with predictions of the temperature saturation, which recent Hall thruster models explain as a transition to space-charge saturated regime of the near-wall sheath. However, in the experiment, the maximum saturation temperature exceeds by almost three times the critical value estimated under the assumption of a Maxwellian electron energy distribution function. The channel narrowing, which should also enhance electron-wall collisions, causes unexpectedly larger changes of the plasma potential distribution than does the increase of the electron temperature with the discharge voltage. An enhanced anomalous crossed-field mobility (near wall or Bohm-type) is suggested by a hydrodynamic model as an explanation to the reduced electric field measured inside a narrow channel. We found, however, no experimental evidence of a coupling between the maximum electron temperature and the location of the accelerating voltage drop, which might have been expected due to the SEE-induced near-wall conductivity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87763/2/057104_1.pd

    Insights on impact from the development, delivery and evaluation of the CLEAR IDEAS innovation training model

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    The increasing pressure on organisations to innovate more effectively in what they deliver and how they work means there is a distinct need for interventions that enhance the innovation capabilities of employees. This paper therefore describes insights from the development, delivery and impact evaluation of a research-based innovation training model (CLEAR IDEAS) designed to improve both the idea generation and idea implementation competencies of trainees. How key findings from the creativity and innovation literature were turned into a practical model and its operationalisation in practice are first discussed. This is followed by presenting a longitudinal evaluation of the training intervention with 151 public sector leaders. Findings showed that the model was well received, led to significant improvements in innovation competencies and resulted in certain trainees undertaking a range of actions to introduce innovations back in the workplace while others failed to apply their learning. Longer-term data provided several examples of subsequent notable ultimate impacts on organisations’ functioning and public service delivery. Finally, reflections on key training, trainee, task and work environment facilitators and inhibitors of innovation training impact are offered

    High-performance liquid chromatography–tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites

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    Applications of tandem mass spectrometry (MS/MS) techniques coupled with high-performance liquid chromatography (HPLC) in the identification and determination of phase I and phase II drug metabolites are reviewed with an emphasis on recent papers published predominantly within the last 6 years (2002–2007) reporting the employment of atmospheric pressure ionization techniques as the most promising approach for a sensitive detection, positive identification and quantitation of metabolites in complex biological matrices. This review is devoted to in vitro and in vivo drug biotransformation in humans and animals. The first step preceding an HPLC-MS bioanalysis consists in the choice of suitable sample preparation procedures (biomatrix sampling, homogenization, internal standard addition, deproteination, centrifugation, extraction). The subsequent step is the right optimization of chromatographic conditions providing the required separation selectivity, analysis time and also good compatibility with the MS detection. This is usually not accessible without the employment of the parent drug and synthesized or isolated chemical standards of expected phase I and sometimes also phase II metabolites. The incorporation of additional detectors (photodiode-array UV, fluorescence, polarimetric and others) between the HPLC and MS instruments can result in valuable analytical information supplementing MS results. The relation among the structural changes caused by metabolic reactions and corresponding shifts in the retention behavior in reversed-phase systems is discussed as supporting information for identification of the metabolite. The first and basic step in the interpretation of mass spectra is always the molecular weight (MW) determination based on the presence of protonated molecules [M+H]+ and sometimes adducts with ammonium or alkali-metal ions, observed in the positive-ion full-scan mass spectra. The MW determination can be confirmed by the [M-H]- ion for metabolites providing a signal in negative-ion mass spectra. MS/MS is a worthy tool for further structural characterization because of the occurrence of characteristic fragment ions, either MSn analysis for studying the fragmentation patterns using trap-based analyzers or high mass accuracy measurements for elemental composition determination using time of flight based or Fourier transform mass analyzers. The correlation between typical functional groups found in phase I and phase II drug metabolites and corresponding neutral losses is generalized and illustrated for selected examples. The choice of a suitable ionization technique and polarity mode in relation to the metabolite structure is discussed as well

    Quantifying the Proteolytic Release of Extracellular Matrix-Sequestered VEGF with a Computational Model

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    BACKGROUND: VEGF proteolysis by plasmin or matrix metalloproteinases (MMPs) is believed to play an important role in regulating vascular patterning in vivo by releasing VEGF from the extracellular matrix (ECM). However, a quantitative understanding of the kinetics of VEGF cleavage and the efficiency of cell-mediated VEGF release is currently lacking. To address these uncertainties, we develop a molecular-detailed quantitative model of VEGF proteolysis, used here in the context of an endothelial sprout. METHODOLOGY AND FINDINGS: To study a cell's ability to cleave VEGF, the model captures MMP secretion, VEGF-ECM binding, VEGF proteolysis from VEGF165 to VEGF114 (the expected MMP cleavage product of VEGF165) and VEGF receptor-mediated recapture. Using experimental data, we estimated the effective bimolecular rate constant of VEGF165 cleavage by plasmin to be 328 M(-1) s(-1) at 25 degrees C, which is relatively slow compared to typical MMP-ECM proteolysis reactions. While previous studies have implicated cellular proteolysis in growth factor processing, we show that single cells do not individually have the capacity to cleave VEGF to any appreciable extent (less than 0.1% conversion). In addition, we find that a tip cell's receptor system will not efficiently recapture the cleaved VEGF due to an inability of cleaved VEGF to associate with Neuropilin-1. CONCLUSIONS: Overall, VEGF165 cleavage in vivo is likely to be mediated by the combined effect of numerous cells, instead of behaving in a single-cell-directed, autocrine manner. We show that heparan sulfate proteoglycans (HSPGs) potentiate VEGF cleavage by increasing the VEGF clearance time in tissues. In addition, we find that the VEGF-HSPG complex is more sensitive to proteases than is soluble VEGF, which may imply its potential relevance in receptor signaling. Finally, according to our calculations, experimentally measured soluble protease levels are approximately two orders of magnitude lower than that needed to reconcile levels of VEGF cleavage seen in pathological situations
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